Transgenic Mouse/Embryonic Stem Cell Shared Resource: Project Summary/Abstract For the past 22 years, the Transgenic Mouse/Embryonic Stem Cell Shared Resource (TMESCSR) has provided a cornerstone for many scientific advances within the Vanderbilt Diabetes Research and Training Center (VDRTC), and elsewhere. Not only have the TMESCSR-derived mice enabled hundreds of highly impactful studies to be performed by VDRTC investigators, they have also been utilized by numerous other non-VDRTC investigators who obtain these animals from public repositories. With the discovery of CRISPR/Cas, which enables the derivation of mice with precisely targeted mutations in a rapid and efficient manner, the TMESCSR made the strategic decision to discontinue its long-standing mouse ES cell (mESC)- based gene targeting service. This action enabled the personnel supporting this resource to optimize and deliver a new CRISPR/Cas-based service, while continuing to provide many other frequently utilized mouse- based services. Together, the services provided by the TMESCSR enable VDRTC members to efficiently derive mice with new genetic alterations, to maintain and cryopreserve existing mouse lines, and to derive new lines from the vast number of mutant mESCs and frozen embryos or sperm that are now available from several large-scale mutagenesis projects, including the Knock-out Mouse Project (KOMP). VDRTC support enables the TMESCSR to import and optimize new technology, such as CRISPR/Cas, thereby assuring that VDRTC investigators have continuing access to up-to-date strategies for deriving state-of-the-art mouse models. These mouse models, in turn, enable VDRTC members to perform high quality studies to understand the pathogenesis of diabetes, obesity and other endocrine diseases, and to perform preclinical testing of new therapies for these diseases, utilizing the expertise in other VDRTC-supported cores (e.g. Cell Imaging Shared Resource, Metabolic Physiology Shared Resource, Hormone Assay and Analytical Services Core).